This application is designed to examine brain properties for placebo responses in chronic back pain patients. We have preliminary data indicating that, in blinded clinical trial studies with neutral instructions regarding treatment, chronic back pain (CBP) and osteoarthritis patients can be subdivided into placebo responders and non- responders and these differences are PREDICTABLE a priori by brain activity. The results imply that CBP placebo response may have clinical utility and that its properties can be studied by human brain imaging techniques. We address these issues in three specific aims, where CBP placebo response properties are studied in a double blind clinical trial (RCT) setting. In Aim 1, we will examine the reproducibility and predictability of the propensity to placebo response in CBP patients. Brain anatomy and function are assessed prior to the start of the RCTs and at different time points during the trial. Additionally, pain and quality of life profilesare collected throughout the trial, using smart phone technology monitoring to acquire these parameters in a naturalistic setting. Brain biomarker outcomes and predictions are contrasted between CBP placebo responders and non- responders, and compared to no treatment. Washout periods are used to test for reversibility of placebo responses. In Aim 2, we study the interaction between placebo and medication treatment, and validate the predictability of placebo propensity in CBP. In Aim 3, we develop a self-report measure to predict placebo propensity based on correlations with neuro-imaging biomarkers. Overall, these studies are designed to critically assess the neurobiology of placebo analgesia for chronic pain within the setting of clinical trials, and creating a readily available clinically useful instrument to identify placebo responders. If successful, the completion of the outlined studies has the potential to dramatically alter health care in chronic pain.